Squalene Based Nanocomposites: A New Platform for the Design of Multifunctional Pharmaceutical Theragnostics
Squalene Based Nanocomposites: A New Platform for the Design of Multifunctional Pharmaceutical Theragnostics
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DOI：
10.1021/nn1034197
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发表时间：
2011-02-01
期刊：
影响因子：
17.1
通讯作者：
Couvreur, Patrick
中科院分区：
文献类型：
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作者：
Arias, Jose L.;Reddy, L. Harivardhan;Couvreur, Patrick
本研究报告了一种新型治疗诊断纳米药物的设计，其结合了（i）在磁场影响下将吉西他滨前药靶向实验性实体瘤的能力与（ii）靶向肿瘤结节的成像。该概念基于将磁铁矿纳米晶体诱导到通过角鲨烯酰吉西他滨（SQgem）生物缀合物的自组装分子构建的纳米颗粒（NP）中。该纳米复合材料的特征在于异常高的载药量、显著的磁化率和低的突释。当注射到L1210皮下小鼠肿瘤模型中时，这些磁铁矿/SQgem NPs被磁性引导，并且它们显示出比其他抗癌治疗（非磁性引导的磁铁矿/SQgem NPs、SQgem NPs或溶液中游离的吉西他滨）大得多的抗癌活性。肿瘤活检的组织学和免疫组织化学研究清楚地证明了磁引导纳米复合材料的治疗优势，而普鲁士蓝染色证实了它们在肿瘤周边的积累。在磁共振成像（Mid）中，使用T-2加权成像已成功观察到优越的上级治疗活性和增强的肿瘤蓄积。通过（i）设计含有T-1 Gd 3+造影剂而不是磁铁矿的基于角鲨烯的NP和（ii）应用于其他抗癌角鲨烯酰，如顺铂、阿霉素和紫杉醇，进一步扩大了这一概念。因此，通过将不同的抗癌药物以及造影剂组合在NP中，我们为癌症治疗和诊断的通用概念框架打开了大门。这种新的治疗不可知的纳米技术平台有望在癌症治疗中有重要的应用。
This study reports the design of a novel theragnostic nanomedicine which combines (i) the ability to target a prodrug of gemcitabine to an experimental solid tumor under the influence of a magnetic field with (ii) the imaging of the targeted tumoral nodule. This concept is based on the indusion of magnetite nanocrystals into nanoparticles (NPs) constructed by self-assembling molecules of the squalenoyl gemcitabine (SQgem) bioconjugate. The nanocomposites are characterized by an unusually high drug loading, a significant magnetic susceptibility, and a low burst release. When injected to the L1210 subcutaneous mice tumor model, these magnetite/SQgem NPs were magnetically guided, and they displayed considerably greater anticancer activity than the other anticancer treatments (magnetite/SQgem NPs nonmagnetically guided, SQgem NPs, or gemcitabine free in solution). The histology and immunohistochemistry investigation of the tumor biopsies dearly evidenced the therapeutic superiority of the magnetically guided nanocomposites, while Prussian blue staining confirmed their accumulation at the tumor periphery. The superior therapeutic activity and enhanced tumor accumulation has been successfully visualized using T-2-weighted imaging in magnetic resonance imaging (Mid). This concept was further enlarged by (i) the design of squalene-based NPs containing the T-1 Gd3+ contrast agent instead of magnetite and (ii) the application to other anticancer squalenoyls, such as, cisplatin, doxorubicin, and paditaxel. Thus, by combining different anticancer medicines as well as contrast imaging agents in NPs, we open the door toward generic conceptual framework for cancer treatment and diagnosis. This new theragnostic nanotechnology platform is expected to have important applications in cancer therapy.